This laboratory is involved in the isolation and characterization of oncogenes. In particular, we are conducting a molecular analysis of action of the ras proteins. Both the immediate and long-range targets of action of these proteins, the "ras pathway," are being determined and the interconnection of this pathway with known pathways is being studied. The yeast S.\cerevisiae has ras genes which are structurally, biochemically, and functionally closely related to the mammalian ras genes. Preliminary work strongly suggests that the yeast ras genes exert their effects by modulating cyclic AMP levels. Studies of the yeast ras will help guide studies of the mammalian ras. In addition, we propose to utilize recent advances in techniques of gene transfer to search for genes which function to restrain cellular proliferation. (Y)